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21 May 2010

Let's play a thought experiment. Imagine that you're a major pharmaceutical company, a public company, with shareholders that you answer to, and market analysts looking over your shoulder to see whether this quarter's earnings are up to projections. Imagine that you want to make a new drug. Let's make it an antibiotic, because — as we talk about here all the time (and SUPERBUG explores in detail) — new antibiotics that can leapfrog over existing drug resistance are very needed. Thus, you imagine, a new antibiotic ought to sell well, even though any individual course of that antibiotic will only be a few weeks by mouth, or maybe a few months by IV if the patient is very sick. You know there's a big market out there.

But: Imagine — as is generally accepted to be true — that it will take about 10 years, and about $1 billion dollars, to get that novel antibiotic through the development pipeline and into the marketplace. And then imagine that — as has been shown for a number of drugs, most recently the new antibiotic daptomycin — bacteria begin developing resistance to your drug within a year of its deployment in patients. And after that, imagine — as has been cited in a number of papers — that once local resistance to your antibiotic appears in approximately 20% of isolates, physicians will cease prescribing your antibiotic, for fear their patient will be one of that 20%.

Would you make that investment? Or would you, if you were a pharma company, opt instead to make insulin, which Type 1 diabetics will take every day for the rest of their lives? Or statins, which at this point we're practically ready to put in the water supply? Or a cancer drug that costs $10,000 per dose? Or Viagra, or Cialis?

If you're a company that is responsible to its shareholders, or listening to its analysts — or even capable of doing basic math — the answer's obvious: Antibiotics lose. Which goes a long way to explaining why so many companies have backed off from making antibiotics, and why many of the few antibiotics in the pipeline are "me too" formulations, rather than new compounds with truly new mechanisms of action.

How to respond to this impasse has been an active debate for a while, largely focused on proposals to give market incentives, changes in tax credits, or patent extensions to pharma companies to persuade them to stay in or re-enter the marketplace. The Infectious Diseases Society of America, the specialty society for infectious-disease physicians (many of whom are also academic researchers), has been addressing this through its campaign "10x 20", which has a goal of getting 10 new compounds into if not through the pipeline by the year 2020.

But, as a new article in the British Medical Journal points out, good incentivizing demands complexity — not just in developing both "push" and "pull" mechanisms (say, tax incentives to fund research v. prizes and wildcard patent extensions), but also in making sure that the incentives can be taken advantage of by companies of all sizes, not just the international mega-pharmas:

The characteristics of an ideal incentive mechanism and the desire for an equitable approach that engages developers of all sizes would suggest that neither push, pull, nor lego-regulatory mechanisms would be optimal to spur the desired investment in antibiotics .... Rather, elements of each should be combined. The exact shape of the ideal package is, however, as yet unclear. (Morel et al.)

And an accompanying editorial emphasizes that new antibiotics are not the only things needed; new diagnostic tests, for instance, need funding as well:

Catchy as 10×20 sounds, the public sector strategy for funding such research and development must prioritise among different health technologies, such as diagnostics and vaccines, to combat antibiotic resistance. For example, three million children die each year from acute respiratory bacterial infections in developing countries, but penicillin sensitive pneumococcal strains have declined to a half, even a quarter, in some countries. A diagnostic test for bacterial pneumonia would save an estimated 405 000 lives a year, by targeting treatment and avoiding overprescription of antibiotics. New vaccines may also reduce reliance on drugs as the use of pneumococcal vaccine has suggested. (So et al.)

This is a hard discussion. I confess, as a longtime reporter, I flinch reflexively at the thought of handing more money to the pharmacos. At the same time, the state of the market demonstrates that the current model is not working. And though I would much prefer we focus on the ecological model of preserving antibiotics as a resource — dialing back on overuse and encouraging rigorous stewardship — it's clear that we'll always need new drugs for the most serious, most resistant infections.

So some sort of incentivizing seems necessary. And the multi-layered approach recommended in the BMJ, with appropriate attention paid to incentivizing the development of tests and vaccines as well, seems worth heeding.

17 May 2010

I'm on the road today and have what feels like seconds between commitments, but there's a brand new piece of research this morning that I think you folks should know about. It's an early-online release from Pediatrics by researchers from 3 states. It uses a database called the Pediatric Health Information Systems analyze diagnosis codes and antibiotic treatment of kids treated for staph at 25 US children's hospitals from 1999 to 2008, and it finds:

The incidence of methicillin-resistant S aureus (MRSA) infections during this period increased 10-fold, from 2 to 21 cases per 1000 admissions, whereas the methicillin-susceptible S aureus infection rate remained stable. Among patients with S aureus infections, antibiotics that treat MRSA increased from 52% to 79% of cases, whereas those that treat only methicillin-susceptible S aureus declined from 66% to <30% of cases. Clindamycin showed the greatest increase, from 21% in 1999 to 63% in 2008.

To translate, for those not used to reading scientific literature:

a 10-fold increase in MRSA diagnoses over 10 years

a 3-fold increase in what was not the most commonly prescribed drug, one useful for the different resistance profile of community infections

clindamycin (used in mild and also invasive infections) eclipsing vancomycin (last-resort drug for invasive cases) as the most-used drug — which could be a sign of changes in prescribing patterns, changes in seriousness of the cases seen, or a warning that with so much use, clindamycin resistance could emerge more quickly, as happened when vancomycin came off the shelf in the 1990s and began to be used more.

It will take me a while to download and read the paper (hard to do in the car), but that's the topline news. Update to come.

16 May 2010

Constant readers: Well, the bug finally got me, or one of its close cousins did. I've been on the road almost nonstop, and after a book event at University of Wisconsin last week, was felled by a violent bout of foodborne illness that was almost certainly staph — not MRSA, but the related strain of staph that causes very rapid food poisoning. (And, umm, thorough. Ick.) So I've been out of commission both physically and mentally. And on a plane again tonight. Back soon in both ways, promise.

But there's important sad news today that I want you all to know about. Revere, the peerless author of the marvelous public health blog Effect Measure, is bowing out of the blogosphere. For more than 5 years now, Revere (a collective voice of an unknown number of public health experts —for simplicity, let's say "he") has been a reliable, thoughtful, expert, humorous and deeply knowledgeable guide to the intricacies of public health and public health politics. He has taken a particular interest in the possibility of pandemic flu and has been the unofficial leader of the loosely knit but fiercely loyal group of bloggers and crowdsourcers who call themselves Flublogia. And though few would admit it, Revere's posts have been consistent agenda-setters in newsrooms all across the planet; insiders knew that, if Revere said something, it would start showing up in newspapers and on wires about 12 hours later.

If you are a Revere reader and missed this news, get over there and leave a note in the quickly lengthening comment string. If you never made the blog's acquaintance, now would not be too soon.

profile

Maryn McKenna is an award-winning journalist and author and a recovering newspaper reporter. She writes about public health, medicine and food policy for national magazines and medical journals, and finds emerging diseases strangely exciting.

SUPERBUG the book

SUPERBUG has been featured on Fresh Air with Terry Gross, NPR's Science Friday, CBC's The Current and other radio and TV as well as numerous print and online publications. Find it at Superbugthebook.com.